Mechanism of androgen receptor action
Gynaecology Research Unit, University Hospitals of Leicester, Victoria Building, Leicester Royal Infirmary, Leicester LE1 5WW, United Kingdom. Maturitas
(Impact Factor: 2.94).
05/2009; 63(2):142-8. DOI: 10.1016/j.maturitas.2009.03.008
Recent research provides a much more detailed understanding of the role of the androgen receptor in normal human development and physiology, its structure, and its functioning. This review discusses genomic and non-genomic actions of the androgen receptor, as well as their co-regulators. We also explore several clinically relevant aspects of the molecular biology of the androgen receptor and its co-regulators.
Available from: Somayeh Assadian
- "It should be noted here that in addition to genomic mode of action of androgens, an increasing body of evidence suggests that androgens can exert rapid, non-genomic effects. This activity typically involves the rapid induction of second messenger signal transduction cascades, including increases in free intracellular calcium, and activation of protein kinase A (PKA), protein kinase C (PKC) and MAPK leading to diverse cellular effects including neuronal plasticity  . "
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ABSTRACT: The effect of testosterone and its metabolites on learning and memory has been the subject of many studies. This study used the Morris water maze task to investigate the effect of intra-hippocampal injection of 3α-diol (one of the metabolites of testosterone) on acquisition stage of spatial memory in adult male rats. During the experiment we observed that 3α-diol, significantly impaired Morris water maze performance in treated rat's compared with controls. Because signaling event mediated by protein kinase A (PKA) especially PKA (II) are critical for many neuronal functions such as learning and memory, the hippocampus was analyzed for mRNA expression of PKA (II) using TaqMan real time RT-PCR. The results indicated that the transcription levels of PKA (II) were significantly decreased in animals treated with 3α-diol compared with controls. Thus, the findings suggest that administration of 3α-diol in hippocampus of adult male rats impairs memory function, possibly via down-regulation of PKA.
Copyright © 2014. Published by Elsevier B.V.
Behavioural Brain Research 11/2014; 280. DOI:10.1016/j.bbr.2014.11.038 · 3.03 Impact Factor
Available from: Gen Yamada
- "c o m / l o c a t e / b b a g r m is organized into functional domains, consisting of an N-terminal domain (NTD), a DNA binding domain (DBD), a C-terminal ligand binding domain (LBD), and a small hinge region between DBD and LBD. The DBD and LBD are highly conserved, whereas the NTD sequence varies among species which may underly different homeostatic control and signaling between species   . The NTD mediates the majority of AR transcriptional activity and is the most active co-regulator interaction surface. "
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ABSTRACT: One of the main functions of androgen is in the sexually dimorphic development of the male reproductive tissues. During embryogenesis, androgen determines the morphogenesis of male specific organs, such as the epididymis, seminal vesicle, prostate and penis. Despite the critical function of androgens in masculinization, the downstream molecular mechanisms of androgen signaling are poorly understood. Tissue recombination experiments and tissue specific androgen receptor (AR) knockout mouse studies have revealed epithelial or mesenchymal specific androgen-AR signaling functions. These findings also indicate that epithelial-mesenchymal interactions are a key feature of AR specific activity, and paracrine growth factor action may mediate some of the effects of androgens. This review focuses on mouse models showing the interactions of androgen and growth factor pathways that promote the sexual differentiation of reproductive organs. Recent studies investigating context dependent AR target genes are also discussed. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 05/2014; 1849(2). DOI:10.1016/j.bbagrm.2014.05.020 · 6.33 Impact Factor
Available from: Sigrid A Lehnert
- "Both native ligands of this receptor, testosterone and DHT bind to AR to activate target gene expression at the transcriptional level. Androgen-AR activity results in the promotion of maintenance and development of male reproduction and male phenotype . The Tex11 gene is also in the same QTL region in chromosome X [29,30], and has previously been reported to be essential for male meiosis and fertility in humans and pigs [32,33]. "
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ABSTRACT: Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69-77 and 81-92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped.
To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential.
Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation.
BMC Genetics 01/2014; 15(1):6. DOI:10.1186/1471-2156-15-6 · 2.40 Impact Factor
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